Molecular Mechanisms of Pesticide Toxicity

The environment represents a key contributor to human health and disease. Exposure to many environmental stressors such as pesticides have detrimental effects on health and are considered to contribute substantially to most diseases of major public health significance. Pesticide toxicity has been clearly demonstrated to alter a variety of physiological functions. In addition, evidence suggests that pesticide exposure increases the risk of cancer and neurodegenerative diseases. Recent evidence also demonstrates the ability of pesticides to act as endocrine disruptors, contributing to various adverse effects associated with reproductive and developmental toxicity (Colborn, 2006; Eskenazi et al., 1999). Thus, it is now evident that research towards understanding how pesticides influence the development and progression of disease will lead to further improvements in public health. A key for Environmental Sciences is identifying and understanding the basic biological processes that are altered or regulated by environmental factors, and that stimulate disease processes to begin, or the course of the disease to be substantially altered. For this, basic biology research with potential for future translation into the clinic must be pursued to understand the fundamental changes caused by exposure to environmental agents especially pesticides that will drive the scientific basis for health decisions. Cells respond and adapt to environmental signals such as toxicants or stressors through multiple mechanisms that involve communication pathways or signal transduction processes. A number of receptors sense the presence of foreign compounds in the cell and induce a cascade of events that is intended to lead to neutralization and excretion of these compounds. However, in many cases the metabolism of xenobiotic substances can give rise to toxic metabolites or to reactive oxygen species (ROS) that can harm the cell further. Additionally, the metabolism of foreign compounds can disturb other essential processes in the body, such as production and metabolism of certain hormones. Alterations in biochemical systems are often more sensitive indicators than those at higher levels of biological organization. Indeed, changes at the molecular level will underlie the effects at higher levels of organization. In this chapter, we focus on a number of molecular pathways implicated in responses to pesticides. In many cases, these responses are adaptive. However, the same systems are involved in reactions leading to toxic effects. They are crucial to the health effects associated with pesticide insult and can be linked to adverse toxic effects and pathologies at higher levels of organization. These systems are: Endocrine disruption that can take place at different physiological levels: A) Altering (inhibiting or stimulating) the secretion of hormones. This possible effect is related to